Studies are in progress on heart transplantation and transplantation rejection using mouse and rabbit models. Cellular reactivity studies using the direct migration inhibition system have shown sensitization to heart and streptococcal membrane antigens during rejections of hearts transplanted in rabbits. Using the mouse model, animals pretreated with certain concentrations of streptococcal membranes and then transplanted have shown prolonged graft survival with no evidence of cellular sensitization or heart-reactive antibody formation. A fraction of the Group A streptococcal membrane has been isolated which will adsrob heart-reactive antibodies. Further studies are in progress to characterize this material and to determine if this is the antigen responsible for the cross-reactivity between streptococcal membranes and heart sarcolemma. Cytotoxicity studies are being done using heart tissue monolayers to determine if the heart-reactive antibody per se is cytotoxic and if the combination of antibody and sensitized lymphocytes blocks or enhances the cytotoxicity of these lymphocytes. The cross-reactive membrane fraction will be used for pretreatment before transplantation to find out if this material can result in prolonged graft survival. Studies will be carried out to ascertain whether the failure to react to the transplanted heart is due to specific tolerance or a general depression of immune responsiveness.